Stabilized particles and methods of preparation and use thereof

ABSTRACT

A method of stabilizing particles with an insulating, semiconducting and/or metallic coating and stabilized particles prepared thereby are disclosed. In addition, particles stabilized by an insulating, semiconducting and/or metallic coating, wherein said coating is attached to said particles via a bifunctional ligand are provided, as is a method is provided for determining the presence of an analyte in a sample comprising incubating the sample with a ligand bound to a coated particle, capable of specifically binding to the analyte and capable of providing a detectable signal and detecting the presence of a ligand-coated particle:analyte complex as indicating the presence of the analyte in the sample.

This is a United States national stage application of Internationalapplication No. PCT/AU98/00896, filed Oct. 28, 1998, the benefit of thefiling date of which is hereby claimed under 35 U.S.C. §120, which inturn claims the benefit of Australian application No. PP 0044, filedOct. 28, 1997, the benefit of the filing date of which is hereby claimedunder 35 U.S.C. §119.

TECHNICAL FIELD

The present invention relates generally to stabilized particles andmethods for their production. More specifically, the present inventionrelates to particles having a size of less than about 0.1 microns or 100nm, such as nanoparticles, that are stabilized by an insulating,semiconducting and/or metallic coating.

BACKGROUND OF THE INVENTION

Nanosized metal particles have a wide variety of potential uses, rangingfrom nonlinear optical switching and high-density information storage toimmunolabeling and tracer diffusion studies in concentrated dispersions.Nanoparticles have unique optical, electrical and magnetic properties.Nanoparticles are typically optically transparent. A major difficultywith large-scale implementation is that metal colloids have complicateddouble-layer structures, and their stability is controlled by bothelectronic equilibria and ionic/polymer adsorption.

Semiconductor materials also have an extraordinary importance intechnology mainly because of their special electronic properties thatarise from a separation between the conduction and valence bands. Whensemiconductor materials are prepared in the nanoparticle-size range, thedensity of electronic states changes in a systematic manner whichstrongly influences the optical and electronic properties of thematerial. The surface of semiconductor nanoparticles is highly defectivefrom the point of view of semiconductor physics, so that energy levelswithin the energy gap of the bulk solid occur due to reconstruction ofatomic positions.

The preparation of at least nanosized particles can be facilitatedgreatly by careful choice of the ligands or stabilizers used to preventparticle coalescence. For example, polymeric stabilizers are veryefficacious dispersants in aqueous solution, whereas long chainsurfactants or chemically specific ligands are more widely used inorganic media. Alternatively, stabilization can be achieved throughcompartmentalization of the particles in micelles or microemulsions,while immobilisation in glasses or sol gels is the preferred techniquewhen redox reactions of the particles with the matrix need to beavoided. More recently, Langmuir-Blodgett (LB) films have been used asparticle stabilizers, and electrodeposition of surfactant-stabilizedmetal particles has been used to create ordered two-dimensionalcrystals. These various techniques not only permit the synthesis of puremetal particles, but also allow the preparation of semiconductorparticles and nanosized alloys, mixed metal particles, and coatedparticles as well as particles with nonspherical geometries (e.g., rodsor platelets).

However, many of the stabilizers employed affect the solid stateproperties of the particles. To circumvent this problem it is desirableto find a stabilizer that prevents particle coalescence. In addition, itis preferable that the stabilizer be chemically inert and opticallytransparent. These conditions can be met by, for example, silica, acoating material used in a wide range of industrial colloid productsranging from paints and magnetic fluids to high quality paper coatings.

The use of silica as a stabilizer rather than an organic molecule hasseveral advantages. In addition to preventing coagulation of theparticles during chemical or electronic processes, the silica shells areexpected to act as a passivant due to a disordered (amorphous) structurethat can be accommodated to that of the underlying particles.

However, some particles, for example, gold metal, have very littleaffinity for silica because they do not form a passivating oxide film insolution. furthermore, there are usually adsorbed carboxylic acids orother organic anions present on the surface of such metals to stabilizethe particles against coagulation. These stabilizers also render themetal surface vitreophobic.

A need exists for a method of coating particles with a suitable agentsuch as silica to impart stability to the particles and to the surfacethereof without substantially affecting their properties, in particulartheir optical properties such as fluorescence.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the invention to address theabove-identified need in the art.

According to one aspect of the present invention there is provided amethod of stabilizing particles with an insulating, semiconductingand/or metallic coating. The method comprises: (i) admixing a source ofparticles with a source of coating to provide a particle-coatingadmixture; (ii) adding to the particle-coating admixture a bifunctionalligand represented by structural formula (I)

A—X—B,  (I)

wherein A is a first functional group that attaches to the particle, orto a coating formed on the particle, selected from the group consistingof thiols, amines, phosphines, phosphates, borates, tetra alkylammoniums, carboxyls, silicates, siloxys, selenates, arsenates andaluminates, B is a functional group that activates the surface of thecore particle for nucleation of a coating layer and is selected from thegroup consisting of thiols, amines, phosphines, carboxyls, silicates,siloxys, silanes, selenates, arsenates and aluminates, and X is anoptional linking group.

In an alternate embodiment, the source of particles is first admixedwith the bifunctional ligand to provide a particle-ligand admixture;(ii) adding to particle-ligand admixture a source of coating; and (iii)allowing the bifunctional ligand and coating to deposit on theparticles.

According to another aspect of the invention, stabilized particles areprovided wherein the particles are prepared by either of theaforementioned methods.

According to yet another aspect of the present invention, there areprovided particles stabilized by an insulating, semiconducting and/ormetallic coating, wherein said coating is attached to said particles viaa bifunctional ligand.

According to still another aspect of the present invention, a method isprovided for determining the presence of an analyte in a samplesuspected of containing the analyte comprising incubating the samplewith a ligand that specifically binds to the analyte and is capable ofproviding a detectable signal, wherein the ligand comprises a coatedparticle as disclosed herein.

According to a further aspect of the present invention there is provideda pigment or paint colourant which is composed wholly or partly of thestabilized particle defined above.

These and other embodiments of the subject invention will readily occurto those of ordinary skill in the art in view of the disclosure herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of the surface reactions involved in providinga silica coating on a core particle using the bifunctional ligand3-mercaptopropyl trimethoxysilane.

FIG. 2 depicts UV-visible spectra of CdS nanoparticles prepared in waterusing sodium silicate as a stabilizer wherein the solid line representsaddition previous to nanoparticle formation and the dashed linerepresents addition after nanoparticle formation.

FIG. 3A is an electron micrographs of silicate-stabilized CdS particlesprepared in water. FIG. 3B is an electron micrograph of silicatestabilized CdS@SiO₂ particles prepared by transfer into ethanol,producing a sudden silica deposition. The scaling of the micrographs isas indicated.

FIG. 4A and FIG. 4B depict UV-visible spectra illustratingphotocorrosion of CdS nanoparticles and Cd@SiO₂ nanoparticles,respectively, after 0 hours (solid line), 24 hours (dashed line) or 48hours (dotted line) of exposure to UV light.

FIG. 5A depicts UV-visible spectra of CdS@SiO₂ nanoparticles calculatedusing Mie theory wherein the dashed and solid lines represent thespectrum for nanoparticles prepared in water and after transfer intoethanol, respectively. FIG. 5B depicts experimentally determinedUV-visible spectra of CdS@SiO₂ particles prepared in water (solid line)and after transfer into ethanol (dashed line).

FIG. 6 depicts a photoluminescence spectrum of CdS@SiO₂ prepared using3-mercaptopropyl trimethoxysilane as a bifunctional ligand.

FIG. 7 depicts electroluminescence spectra observed from CdS@SiO₂particles prepared using 3-mercaptopropyl trimethoxysilane asbifunctional ligand.

DETAILED DESCRIPTION OF THE INVENTION

The practice of the methods of the present invention will employ, unlessotherwise indicated, conventional techniques of synthetic organicchemistry that are within the skill of the art. Such techniques areexplained fully in the literature. See, e.g., Kirk-Othmer's Encyclopediaof Chemical Technology; House's Modern Synthetic Reactions and C. S.Marvel and G. S. Hiers' text, ORGANIC SYNTHESIS, Collective Volume 1.

As used in this specification and the appended claims, the singularforms “a,” “an” and “the” include plural references unless the contentclearly dictates otherwise. Thus, for example, reference to a“functional group” includes more than one such group, reference to “acoating layer” includes more than one such layer, and the like.

A. Definitions

In describing the present invention, the following terms will beemployed, and are intended to be defined as indicated below.

The term “alkyl” as used herein refers to a branched or unbranchedsaturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl,tetradecyl, hexadecyl, eicosyl, tetracosyl and the like, as well ascycloalkyl groups such as cyclopentyl, cyclohexyl and the like. The term“lower alkyl” intends an alkyl group of 1 to 6 carbon atoms, preferably1 to 4 carbon atoms.

The term “alkenyl” as used herein refers to a branched or unbranchedhydrocarbon group of 2 to 24 carbon atoms containing at least onecarbon-carbon double bond, such as ethenyl, n-propenyl, isopropenyl,n-butenyl, isobutenyl, t-butenyl, octenyl, decenyl, tetradecenyl,hexadecenyl, eicosenyl, tetracosenyl and the like. Preferred alkenylgroups herein contain 2 to 12 carbon atoms and 2 to 3 carbon-carbondouble bonds. The term “lower alkenyl” intends an alkenyl group of 2 to6 carbon atoms, preferably 2 to 4 carbon atoms, containing one —C═C—bond.

The term “alkynyl” as used herein refers to a branched or unbranchedhydrocarbon group of 2 to 24 carbon atoms containing at least one —C≡C—bond, such as ethynyl, n-propynyl, isopropynyl, n-butynyl, isobutynyl,t-butynyl, octynyl, decynyl and the like. Preferred alkynyl groupsherein contain 2 to 12 carbon atoms. The term “lower alkynyl” intends analkynyl group of 2 to 6, preferably 2 to 4, carbon atoms, and one —C≡C—bond.

The term “halogen” as used herein refers to fluorine, chlorine, bromineand iodine.

A coated particle depicted, for example, as “CdS@SiO₂” is intended torefer to a core particle comprising CdS having a coating comprisingSiO₂.

The term “bifunctional ligand” is used herein in its broadest sense torefer to any mono- or polydentate ligand comprising a first functionalgroup capable of binding to a particle and a second functional secondcapable of binding to the coating. Preferably, the first functionalgroup attaches to a particle and the second functional group attaches toa coating via one or more attachment points. Optionally, thebifunctional ligand may comprise a spacer between the first and secondfunctional groups.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances where itdoes not. For example, the phrase “optionally substituted lower alkyl”means that the lower alkyl group may or may not be substituted and thatthe description includes both unsubstituted lower alkyl and lower alkylwhere there is substitution.

A stabilized particle and method of preparing stabilized particles areprovided herein. Stabilization of the particles is achieved by providinga coating on the particle that is insulating, semiconducting, metallicor combinations thereof. The coating is attached to the particle througha bifunctional ligand comprising a first functional group and a secondfunctional group.

The particle is preferably a nanoparticle having a size of less thanabout 0.1 microns, i.e., 100 nanometers. Preferably the particles have adiameter less than 40 nm. Larger particles may suffer from sedimentationproblems during the coating process. The particles may vary in shapefrom generally spherical, through ellipsoid to cylindrical or rod like.For non spherical particles the effective diameter is (abc)^(⅓) where a,b and c are the coordinate axes of the particles. Accordingly, forrod-like particles where a=b<<c, the length (c) of the rods may exceed100 nm provided (abc)^(⅓) is less than 100 nm. Preferably (abc)^(⅓) isless than 20 nm to obtain optical transparency. There may be adistribution of particle size and in this specification we refer todiameters as the number average. Relatively narrow size distributionsare preferred as a small proportion of large particles may causeundesirable light scattering or sedimentation. The particle can comprisea metal, such as copper, silver, gold, platinum, or the like, or a metalcompound or alloy such as a metallic sulphide, a metallic arsenide, ametallic selenide, a metallic telluride, a metallic oxide, a metallichalide or a mixture thereof. Preferred particles are semiconductornanoparticles. Examples of semiconductor nanoparticles include cadmiumsulphide (CdS), germanium (Ge), silicon (Si), silicon carbide (SiC),selenium (Se), cadmium selenide (CdSe), cadmium telluride (CdTe), zincsulphide (ZnS), zinc selenide (ZnSe), zinc oxide (ZnO) and the like.These semiconductor nanoparticles are known to exhibit strongphotoluminescence in the visible range of the electromagnetic spectrum.Some organic polymers, such as poly(pyrrole), also form conductingfluorescent particles and precipitate as nanoparticles. Such polymernanoparticles can also be stabilized using the method disclosed herein.

The source of the particles may be either the particles per se, acompound containing the particles or two or more compounds which whencombined form the particles. For example, Cd(NO₃)₂ and Na₂S may becombined to form the semiconductor CdS. In the case of metal cores, thesource of the particles is usually a metal salt that can be reduced toform metal particles with desired size and morphology, for example,AuCl₄ ⁻ is a source of gold particles and AgNO₃ is a source of silverparticles. The particles to be coated may already be of a core/shellstructure or a coat cored structure. In this case the particles cantherefore have multiple coating layers.

The particle is coated with a coating layer. Preferably the coatingthickness is between 10 and 30 nm. At coating thicknesses less than 10nm coated particles may exhibit some colloidal instability. If coatingthickness significantly exceeds 30 nm the coated particles may causeundesirable light scattering. Preferably the coated particles are alsonanoparticles. The coating is bonded to the particle through abifunctional ligand. The bifunctional ligand is represented by theformula:

A—X—B

wherein A, B and X are defined as above.

The first functional group, A, is a chemical entity or group that canbind specifically to a particle and therefore alter the surface stateand surface trap energies that control or affect surface fluorescenceand nonradiative decay pathways in photoexcited nanoparticles. The firstfunctional group can be monodentate or polydentate, which may enhancebonding to the particle. It will be understood that the first functionalgroup chosen will depend on the type of particle being coated. Thestructure of the first functional group may also change when it is boundto the surface of the particle. For instance, when the first functionalgroup is —NH₂, then only N bonds to the particle surface. In the case of—SH, only S bonds to the particle surface. The first functional groupcan be selected so as to bind to a particle that has been coatedaccording to the method disclosed herein, thereby providing a particlecomprising more than one coating layer.

The second functional group is a chemical entity or group which has theability to activate the surface of the core particle for nucleation of acoating layer. The second functional group may also activate thefluorescence in the coating layer. It will be appreciated that thesecond functional group chosen will depend on the type of coating to bedeposited. For example, silane second functional groups activators areusually negatively charged in water at a pH of greater than two. Acationic second functional group such as NR₄ ⁺, wherein R is an alkylgroup such as methyl or ethyl may be more efficacious for deposition ofanionic coating species such as AuCl₄ ⁻, PtCl₆ ²⁻ or SnO₃ ²⁻. In somecases, it may be useful to apply an organic coating such as a conductingpolymer to the surface to aid electron transfer from the activated coreparticle. In this case, the second functional group could be anunsaturated ethylene or allyl group which can couple to the alkyl chainsof the polymer coating. The activating group will then be optimized forcoupling to any functional groups on the backbone or on pendent groupsof the polymer coating. A bifunctional ligand comprising such a coatingactivator will permit activated core particles to be coated withconducting layers that can be embedded into organic films such asplastics.

Suitable spacers include, but are not limited to, straight chain,branched or cyclic hydrocarbons such as alkyl, alkenyl or alkynylspacers that optionally can be substituted with halide groups such asfluoride, chloride, bromide or iodide. Preferably, the spacer is analkyl or fluoroalkyl chain.

Specific examples of bifunctional ligands include are 3-mercaptopropyltrimethoxysilane [SH(CH₂)₃ (Si(OMe)₃)] (“MPS”), 1,3-propanedithiol[(HS(CH₂)₃SH)₂], 3-aminopropanethiol [(HS(CH₂)₃NH₂)] (“APT”) and 3-aminopropyl trimethoxysilane [NH₂(CH₂)₃Si(OMe)₃] (“APS”). In one preferredembodiment, the bifunctional ligand is MPS, APT or APS. In theseligands, the mercapto or thiol and amino groups function as the firstfunctional group and the trimethoxysilane group functions as the secondfunctional group. In an other preferred embodiment the second functionalgroup may be another alkoxysilane group such as (Si(OEt)₃ or any otherhydrolysable functional group such as Si (OPr)₃. In other words thesecond functional group can be a hydrolysable functional group havingthe structural formula (Si(OR)₃), wherein R is an alkyl group,preferably a lower alkyl group. While in this specification the Examplesillustrate R being a methyl group other alkyl, especially lower alkylgroups could also be used to provide suitable coatings. The propyl groupacts as a spacer. When the activator is HS(CH₂)₃SH, the core particlewill be activated by the SH groups and its surface will also be coatedwith those groups which bind strongly to most metal ions including Cd²⁺and Ag⁺. This surface is then suitable for nucleation of a metal sulfidecoating such as CdS, CdSe or ZnSe or a metal coating per se such as Agor Au.

It will be appreciated that the coating may be selected from the samematerial as the core particles. Suitable insulating, semiconductingand/or metallic coatings include silica, Se, organic conducting polymerssuch as poly(pyrrole), metal oxides such as titania (TiO₂), zirconia(ZrO₂), alumina (Al₂ O₃), zinc oxide (ZnO), tin dioxide (SnO₂) ormanganese oxide (MnO), metal sulphides such as CdS and ZnS, metalselenides such as CdSe and ZnSe, metal tellurides such as CdTe and ZnTe,metal halides such as silver iodide (AgI) and silver bromide (AgBr),catalytically active metals such as platinum, palladium, iridium oralloys and mixtures thereof, metals with unusual optical properties suchas bismuth or metals per se such as copper, silver or gold. Silica is apreferred coating due to its ability to dissolve in various solvents andresistance to coagulation. The coating is preferably homogeneous andmicroporous which protects the particles for example from photochemicaldegradation. However, it will be understood that the tern “coating” isused herein in its broadest sense and refers to both partial andcomplete coatings, as well as to multiple layers of coatings. While acomplete coating is desirable, it may not be possible as a consequenceof experimental limitations or because the required effect is achievablewith an incomplete coating.

The source of the coating may be either the coating per se, a compoundcontaining the coating or two or more compounds which when combined formthe coating. When the coating is silica, sodium silicate may be anappropriate source. Addition of Cd²⁺ and H₂Se at an optimal rate toactivated particles will generate particles coated with CdSe.Alternatively, slow reduction of AuCl₄ ⁻ can be used to coat particleswith gold onto the mercapto-activated surface described above.

For metal oxide or hydroxide coatings, control of pH can be used tooptimize the coating conditions. When coating with silica, depositionoccurs optimally at a pH of about 9 to about 12. The silane activatorligand is then negatively charged, which favors the deposition ofcationic species. However, very high pH often causes precipitation ofmetal hydroxide or oxide so quickly that the coating cannot compete. Forexample, in the case of alumina or titania deposition ontosilane-activated core particles, a lower pH may provide slowerhydrolysis and less nucleation of pure coating particles at the expenseof weakening the attraction between the silane groups and the metalcations in solution. An optimal pH exists which minimizes separatecoating particle formation whilst maximizing deposition onto theactivated surface. For metal oxide coatings such as Al₂O₃, TiO₂, ZrO₂and SnO₂, silane groups are the simplest and cheapest activator to use,but specially synthesized activators containing, for example, Ti, Al orSn alkoxide groups as coating activators may be more efficacious.

The surface reactions involved in attaching silica to MPS areillustrated in FIG. 1.

The first two steps of the method disclosed and claimed herein comprise(i) reacting a source of particles with a source of coating and (ii)adding a bifunctional ligand of the formula A—X—B wherein A, X, and Bare as defined above. Alternatively, the source of particles may firstbe reacted with the bifunctional ligand, followed by addition of thecoating. These first two steps may be carried out in any suitablesolvent, preferably water and/or an alcohol such as ethanol. Theparticle size may be influenced by the order of addition of thereagents. Each reagent is generally added with stirring using anysuitable known technique, for example, magnetic stirring. After theparticle, bifunctional reagent and coating are admixed, the bifunctionalligand and coating are allowed to deposit onto the particle. Theduration of the deposition step may be from about 6 hours to about 7days so as to ensure that the coating has deposited onto the modifiedparticle surface.

The coated particles may then be transferred into a suitable solventsuch as an alcohol, e.g., ethanol, so that any excess dissolved coatingthat may be present precipitates out onto the coated particle therebyincreasing the thickness of the coating thereon.

In another embodiment, the method described in Stöber et al. (1968) J.Colloid Interface Sci.26:62 can be used for further coating growth whenthe coating is silica. Briefly, this technique involves thebase-catalyzed hydrolysis of tetraethoxysilane (“TES”) and subsequentcondensation/polymerization of silica monomers onto the existing coatedparticles.

The stabilization of the particles of the present invention inside acoating preserves their unique properties such as fluorescence. Inaddition, the coating substantially prevents photochemical degradationof the particles which can be advantageous in high temperature oroptical applications. The coating may also enable these particles to bedispersed in a wide variety of matrices including glasses, polymers andsolvents.

Coated particles as disclosed and claimed herein find utility asdetectable labels for use in a variety of contexts. For example, amethod is provided for determining the presence of an analyte in asample suspected of containing the analyte comprising incubating thesample with a ligand that specifically binds to the analyte and iscapable of providing a detectable signal by virtue of the presence of acoated particle as part of the ligand. The ligand can be any moleculethat can specifically bind to the analyte. Thus, the ligand can be anantigen- or epitope-specific monoclonal or polyclonal antibody, a poly-or oligonucleotide comprising a nucleic acid sequence complementary tothe nucleic acid sequence of a poly- or oligonucleotide analyte, areceptor agonist or antagonist capable of binding specifically to acellular receptor molecule, e.g., a cell surface receptor molecule, acytoplasmic receptor molecule, a nuclear receptor molecule, or the like.The coated particle can be attached to the ligand using methods that arewell known in the art.

A coated particle-ligand composition is added to the sample andincubated therewith for a period of time sufficient for the coatedparticle-ligand to bind to the analyte to form a coatedparticle-ligand:analyte complex. The amount of coated particle-ligandcomposition and the period of time required for the coatedparticle-ligand composition to bind to the analyte can be determinedusing any method routine in the art. The coated particle-ligand:analytecomplex can be separated from unbound coated particle-ligand compositionusing methods such as filtration, centrifugation and the like. Thepresence of a coated particle-ligand:analyte complex can be detectedusing fluorescence, photoluminescence, absorption, diffraction orscattering methods. The amount of coated particle-ligand:analyte complexdetected can be quantitated by comparison with a standard curve preparedusing samples containing known concentration of the analyte.

Possible additional applications for these stabilized particles may bein the fields of pigments, paints, fabrics, optics such as fluorescenceand electronics.

Below are examples of specific embodiments for carrying out the presentinvention. The examples are offered for illustrative purposes only, andare not intended to limit the scope of the present invention in any way.

Efforts have been made to ensure accuracy with respect to numbers used(e.g., amounts, temperatures, etc.), but some experimental error anddeviation should, of course, be allowed for.

General Experimental

Tetraethoxysilane (“TES”), sodium silicate (Na₂O(SiO₂)₃₋₅ (27 wt. %SiO₂) were purchased from Aldrich. Cd(NO₃)₂ (Merck), Na₂S (Sigma) and3-mercaptopropyl trimethoxysilane (MPS) were used. Technical gradeethanol (Panreac) and distilled water were used in all the preparations.

Transmission electron microscopy (“TEM”) was carried out using a PhilipsCM20 microscope operating at 200 kV. Samples were prepared by allowing adrop thereof to evaporate on top of a carbon-coated copper grid.UV-visible spectra were measured with a HP 8453 diode arrayspectrophotometer in 1-cm path length quartz cuvettes.

EXAMPLE 1 Preparation and Characterization of a CDS Particle Coated withSilica

The general procedure for the preparation of CdS@SiO₂ colloids comprisedthe following steps.

To 45 mL of distilled water, 2.0 mL of Cd(NO₃)₂ 10⁻² M, 2.5 mL Na₂ S8×10⁻³ M and 0.25 mL of 1 wt. % sodium citrate solution were added undervigorous stirring and a nitrogen atmosphere. The final CdS particleconcentration was 0.4 mM.

To 50 mL of the CdS solution was added 0.5 mL of a freshly preparedaqueous solution of MPS (1 mM) under vigorous magnetic stirring. Sodiumsilicate (2.0 mL of a 0.54 wt. % solution, pH 10.5) was added, againunder vigorous stirring. The resulting dispersion (pH>8.5), particlesize 5-10 nm, was allowed to stand for 5 days, so that silica slowlypolymerized or formed onto the modified CdS particle surface. Thedispersion of silica-coated CdS particles was transferred into ethanol,so that the excess dissolved silicate precipitated out (mainly on theexisting cores), increasing the shell thickness.

The method described in Stober et al., supra, was then used for furthergrowth. This method comprised the base-catalyzed hydrolysis of TES andsubsequent condensation/polymerization of silica monomers onto theexisting nuclei.

A. Stabilization with Citrate

Citrate ions have been used as protective agents for a variety ofinorganic colloids. Different citrate/Cd²⁺ concentration ratios weretested, finding an optimal value of 0.45, which was used for all theremaining experiments. The average particle size of the CdS particlesobtained through this process was 7 nm.

CdS can be degraded under the influence of light in the presence ofdissolved oxygen. The action of oxygen consists of an oxidation ofsulphide radicals arising through the formation of hole-anion pairs atthe particle surface:

S_(S) ⁻+O₂→S_(S)+O₂ ⁻  (I)

wherein subscript s indicates a surface atom.

This process can be inhibited through the addition of excess sulphideions, although an alternative and cleaner way is to carry out thereaction under nitrogen atmosphere. When the synthesis is performed inthe absence of oxygen, i.e., under a nitrogen atmosphere, the colloidprepared is stable against photodegradation for weeks, allowing formodifications to be performed on it without further precautions.

B. The Role of MPS

The adhesion of silicate moieties at the particle surface can only bemade effective when a silane coupling agent is present in the solution.Such a coupling agent acts as a surface primer for making the colloidsurface vitreophilic and facilitating silicate deposition.

In the case of a particle of CdS, MPS was chosen since it contains amercapto group that can bond directly to surface Cd sites, leaving thesilane groups pointing toward solution, from where the silicate ionsapproach the particle surface. These silicate ions build up a firstsilica shell which permits the transfer into ethanol without particlecoagulation. It was observed that the presence of a very thin silicashell is not sufficient to prevent photodegradation, which is mainlyattributed to the presence of pores which are large enough to permit thediffusion of O₂ molecules through them.

C. Transfer into Ethanol

The solvent exchange process plays two important roles: on the one handit serves to precipitate out all the silicate moieties (monomers oroligomers) still present in the solution due to a sudden decrease insolubility and on the other hand, it is necessary for the growth ofthicker shells when desired. An appropriate ethanol:water volume ratio(at which maximum silicate deposition on the cores is achieved whilstspontaneous nucleation of silica particles is minimised) was found to bebetween about 4:1 and about 5:1.

D. Transmission Electron Microscopy

FIG. 3 shows the appearance under the TEM of the particles preparedfollowing the method described. The slightly higher electron absorptionby CdS than by SiO₂ provides a sufficient contrast to show the corehomogeneously surrounded by the silica shell. As shown in FIG. 3, thecrystalline nature of the CdS particles can be observed, in contrastwith the amorphous silica shell. Both core-free and multiple-core silicaparticles are formed as well during the transfer into ethanol. The shellcan be made thicker and the particle surface smoother by the addition ofammonia and TES, resulting in monodisperse silica spheres with CdS coresplaced at their centers.

E. Stabilization Against Photodegradation

Silica-coated particles are far more stable against photodegradationthan uncoated particles, so that samples could be stored in light forseveral weeks with negligible variation of their absorption spectra. Asan example, FIG. 5 shows the time evolution of the spectra of thecitrate-stabilized particles, as compared with silica-coated ones. Thiseffect can be related to the small pore size of the silica shells grownin ethanol through monomer addition which makes it very difficult for O₂molecules to reach the particle surface. Such a protection would be ofgreat importance in the preparation of stable nanostructured materialswith practical applications.

F. Optical Properties of Silica-Coated CdS

The optical properties of dispersions of spherical particles can bepredicted by Mie theory (M. Kerker, The Scattering of Light and OtherElectromagnetic Radiation (Academic Press, New York, 1969)). Accordingto this theory, the extinction coefficient of the dispersion at a givenwavelength depends on the complex dielectric constant of the particlesat that wavelength and on the refractive index of the solvent. Particlesize is a parameter with special significance for metal andsemiconductor particles, which show quantum size effects.

When Mie theory is adapted to core-shell particles, the dielectric datafor both the core and the shell materials need to be taken into account.For silica, only the real component of the dielectric constant wasconsidered, using the square of the refractive index (1.456). Thespectra for bare CdS spherical particles were calculated with a diameterof 6 nm and of the same particles surrounded by a 5 nm thick silicashell. These spectra are compared in FIG. 5 with the experimentalspectra of samples obtained by transfer into ethanol of small CdSparticles and subsequent growth with TES. The agreement between bothplots is fairly good, showing for the silica-coated particles anincreased extinction mainly at wavelengths lower than the absorptiononset and showing that the optical properties of the CdS particles areneither significantly altered by Silica deposition, nor that the silicadeposition when carried out as described herein leads to significantcoalescence or aggregation. This is also confirmed by the results setout in FIG. 2.

G. Electroluminescence

In FIG. 6, the photoluminescence spectrum of CdS@SiO₂ particles isshown. The excitation wavelength is 400 nm. A strong, broad peak with amaximum intensity at 580 nm was observed. This is attributed to therecombination of trapped charge carriers in surface states at theCdS-silica interface. The density of surface states has beendramatically enhanced by the adsorption of MPS, yielding strongfluorescence readily visible to the human eye. These coated particlescan be concentrated by rotary evaporation to form more viscous solutionor, if required, can be made more viscous by addition of polymers suchas poly(vinyl) alcohol, poly(vinyl) acetate or poly(acrylic) acid.However, this affects only the deposition conditions and is notcritical.

A colloid film is prepared by applying such a viscous polymericpreparation to indium tin oxide (ITO) glass (1 cm×1 cm) on a spin coater(1000 rpm) via a micropipette. Other coating methods such as dipcoating, screen printing or spray coating may also be used. The film canbe made thicker by drying the coated particles in an oven at <100° C.and then reapplying second or multiple coatings. Optimal volumes andspin speeds depend on the exact viscosity of the colloid solutionapplied.

Electroluminescence was demonstrated by polarizing the ITO electrodecoated with a thin film of CdS@SiO₂ particles in a solution of potassiumpersulfate (1 M) at pH 13. The solution also contained a Ag/AgClreference electrode and a platinum flag counter electrode. As thepotential of the ITO electrode is made more negative, light is observedfrom the electrode as shown in FIG. 7. The intensity increases as thepotential is made more negative. The intensity depends in a complicatedway on applied voltage, electrode resistance and solution composition.Electroluminesence spectra at three potentials are shown. These spectraindicate that the coating, while protecting the particles fromcoalescence, still allows charge transfer and electroluminescenceprocesses to proceed at the surface of the particles. The silica coatingallows the particle size and fluorescence properties of the particlefilm to be tailored to yield optimal colour and efficiency and thencoated without affecting the particle characteristics. By maintainingthe small sizes, light scattering from the particle film and theassociated intensity losses are also minimized.

EXAMPLE 2 Preparation and Characterization of a SE Particle Coated withSilica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that selenium (Se) wassubstituted for CdS. The Se@SiO₂ nanoparticles had properties similar tothose determined for CdS@SiO₂ particles.

EXAMPLE 3 Preparation and Characterization of a SI Particle Coated withSilica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that silicon (Si) wassubstituted for CdS. The Si@SiO₂ nanoparticles were expected to haveproperties similar to those determined for CdS@SiO₂ particles.

EXAMPLE 4 Preparation and Characterization of a CD SE Particle Coatedwith Silica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that cadmium selenide (CdSe)was substituted for CdS. The CdSe@SiO₂ nanoparticles had propertiessimilar to those determined for CdS@SiO₂ particles.

EXAMPLE 5 Preparation and Characterization of a CD TE Particle Coatedwith Silica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that cadmium telluride (CdTe)was substituted for CdS. The CdTe@SiO₂ nanoparticles had propertiessimilar to those determined for CdS@SiO₂ particles.

EXAMPLE 6 Preparation and Characterization of a ZNS Particle Coated withSilica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that zinc sulfide (ZnS) wassubstituted for CdS. The ZnS@SiO₂ nanoparticles had properties similarto those determined for CdS@SiO₂ particles.

EXAMPLE 7 Preparation and Characterization of a ZNSE Particle Coatedwith Silica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that zinc selenide (ZnSe) wassubstituted for CdS. The ZnSe@SiO₂ nanoparticles had properties similarto those determined for CdS@SiO₂ particles.

EXAMPLE 8 Preparation and Characterization of a ZNO Particle Coated withSilica

A coated semiconductor nanoparticle was prepared according to the methoddescribed in Example 1, with the exception that zinc oxide (ZnO) wassubstituted for CdS. The ZnO@SiO₂ nanoparticles had properties similarto those determined for CdS@SiO₂ particles.

EXAMPLE 9 Preparation and Characterization of an AgI Particle withSilica

A 100 mL solution containing KI (8×10⁻⁴ M) and sodium citrate (1 mM) wasprepared and stirred rapidly using a magnetic stirrer. A solution of 5mL 0.01M of AgNO₃ was added by pipette. The solution immediately turnedfrom clear to transparent yellow, indicating the formation of small AgIcrystallines. Within 5 minutes, APS (1 mM, 0.5 mL) is added. After 20minutes, active silicate ion was added, prepared as outlined before. Athin shell of silica was deposited after 24 hours.

EXAMPLE 10 Preparation and Characterization of an Au Particle Coatedwith Silica

Au particles from 40-80 nm in diameter were grown from seed particlesprepared via the Turkevich method. (Enüstün B. V.; Turkevich, J J.Am.Chem.Soc. 1963 85 3317).

Seed Gold Sol

100 mL of 0.5 mM HAuCl₄ was heated with mild stirring until boiling. Aboiling solution of 5 mL 0.5 mM tri-sodium citrate was added to theHAuCl₄ solution with rapid stirring. The resulting solution was thenboiled for approximately 15 minutes with stirring. Finally, the solutionwas allowed to cool.

Large Particles

A 50 mL solution containing 25 nM 15 nm Au colloid and 1.5 mL NH₂OH.HClwas prepared. 3 drops 1M KOH was added to 70 mL of 1 mN HAuCl₄, raisingthe pH from approximately 3 to 4. 50 mL of HAuCl₄ solution was addeddropwise (at a rate of approximately one drop every two seconds) to theAu colloid solution with stirring.

The new particle volume was calculated from the initial and final goldion concentrations and the initial particle size. Such particles arelarge, reasonably spherical though they contain angular and rod likeparticles. They are purple in transmitted light but scatter yellow lightstrongly. They settle out of solution over hours if left standing. Thesurfaces have both adsorbed citrate and adsorbed hydroxylamine, whichare displaced by APS. Coating is effected by the procedure of Example 1.

EXAMPLE 11 Preparation of an Au Particle with a SNO₂ Coating

The APS also enhances deposition of other oxide coatings. Particularlyimportant are conducting or semiconducting layers, which allow electrontransport between the core and exterior.

10 mL of 0.045M Na₂SnO₃.3H₂O was acidified to pH 10.5 by addition of 3drops 1M nitric acid. 25 μL of 1 mM APS was added to 5 mL of 0.5 mM 15nm Au colloid dropwise with stirring. 15 minutes later, 1 mL of thestannate solution was added to the Au colloid solution with stirring. Acolour change became apparent in the solution after one week.

The colour of the ruby red gold sol turned a purple-crimson as coatingtook place. The coating obtained this way was about 5-10 nm thick, andwas dependent on the ageing time, the pH of ageing and the stannate ionconcentration. It also depended on the gold colloid concentration andthe stirring rate.

Accordingly, stabilized nanoparticles and methods for preparingstabilized nanoparticle have been disclosed. Although preferredembodiments of the subject invention have been described in some detail,it is understood that obvious variations can be made without departingfrom the spirit and the scope of the invention as defined by theappended claims.

What is claimed is:
 1. A method for preparing a coated particle,comprising: (i) admixing a source of the particle with a source ofcoating to provide a particle-coating admixture; (ii) adding to theparticle-coating admixture a bifunctional ligand having structuralformula (I): A—X—B wherein A is a first functional group that attachesto the particle, or to a coating formed on the particle, B is a secondfunctional group that activates the surface of the core particle fornucleation of a coating layer and X is an optional linking group; and(iii) allowing the bifunctional ligand and coating to deposit on theparticle.
 2. A method for preparing a coated particle, comprising: (i)admixing a source of the particle with a bifunctional ligand havingstructural formula (I): A—X—B wherein A is a first functional group thatattaches to the particle, or to a coating formed on the particle, B is asecond functional group that activates the surface of the core particlefor nucleation of a coating layer and X is an optional linking group, toprovide a particle-ligand admixture; (ii) adding to particle-ligandadmixture a source of coating; and (iii) allowing the bifunctionalligand and coating to deposit on the particle.
 3. The method of claim 1or claim 2, wherein the particle is a nanoparticle.
 4. The method ofclaim 3, wherein the nanoparticle comprises a metal or a metal compound.5. The method of claim 4, wherein the nanoparticle comprises a metalselected from the group consisting of copper, silver, gold and platinum.6. The method of claim 4, wherein the nanoparticle comprises a metalcompound selected from the group consisting of a metallic sulfide, ametallic arsenide, a metallic selenide, a metallic telluride, a metallicoxide, a metallic halide and a mixture thereof.
 7. The method of claim3, wherein the nanoparticle is a semiconductor nanoparticle.
 8. Themethod of claim 7, wherein the semiconductor nanoparticle comprisescadmium sulfide (CdS), germanium (Ge), silicon (Si), silicon carbide(SiC), selenium (Se), cadmium selenide (CdSe), cadmium telluride (CdTe),zinc sulfide (ZnS), zinc selenide (ZnSe) or zinc oxide (ZnO).
 9. Themethod of claim 1 or claim 2, wherein A is selected from the groupconsisting of a thiol, an amine, a phosphine, a phosphate, a borate, atetra alkyl ammonium, a carboxyl, a silicate, a siloxyl, a selenate, anarsenate and an aluminate.
 10. The method of claim 1 or claim 2, whereinB is selected from the group consisting of a thiol, an amine, aphosphine, a carboxyl, a silicate, a siloxyl, a silane, a selenate, anarsenate and an aluminate.
 11. The method of claim 1 or claim 2, whereinX is present and is a straight chain, branched or cyclic hydrocarbonselected from the group consisting of alkyl, alkenyl and alkynyl,optionally substituted with a fluoride, chloride, bromide or iodide. 12.The method of claim 1 or claim 2, wherein the bifunctional ligand isselected from the group consisting of 3-mercaptopropyl trimethoxysilane[SH(CH₂)₃(Si(OMe)₃)] (MPS), 1,3-propanedithiol [(HS(CH₂)₃SH)]3-aminopropanethiol [(HS(CH₂)₃NH₂)] (APT) and 3-aminopropyltrimethoxysilane [NH₂(CH₂)₃Si(OMe)₃] (APS).
 13. The method of claim 1 orclaim 2, wherein the source of coating is selected from the groupconsisting of silica (SiO₂), Se, an organic conducting polymer, a metal,a metal oxide, a metal sulphide, a metal selenide, a metal telluride,and a metal halide.
 14. The method of claim 13, wherein the source ofcoating is silica.
 15. The method of claim 13, wherein the source ofcoating is a metal oxide selected from the group consisting of titania(TiO₂), zirconia (ZrO₂), alumina (Al₂O₃), zinc oxide (ZnO), tin dioxide(SnO₂) or manganese oxide (MnO).
 16. The method of claim 13, wherein thesource of coating is a metal sulfide selected from the group consistingof CdS and ZnS.
 17. The method of claim 13, wherein the source ofcoating is a metal selenide selected from the group consisting of CdSeand ZnSe.
 18. The method of claim 13, wherein the source of coating is ametal telluride selected from the group consisting of CdTe and ZnTe. 19.The method of claim 13, wherein the source of coating is a metal halideselected from the group consisting of silver iodide (AgI) and silverbromide (AgBr).
 20. The method of claim 13, wherein the source ofcoating is a metal selected from the group consisting of platinum,palladium, iridium, bismuth, copper, silver, gold, and alloys andmixtures thereof.
 21. A coated particle prepared according to any one ofclaims 1 to
 20. 22. A particle stabilized by a coating, wherein saidcoating is attached to said particle via a bifunctional ligand havingstructural formula (I): A—X—B wherein A is a first functional group thatattaches to the particle, or to a coating formed on the particle, B is asecond functional group that activates the surface of the core particlefor nucleation of a coating layer and X is an optional linking group.23. The particle of claim 22, wherein the particle is a nanoparticle.24. The particle of claim 23, wherein the nanoparticle comprises a metalor a metal compound.
 25. The particle of claim 24, wherein thenanoparticle comprises a metal selected from the group consisting ofcopper, silver, gold and platinum.
 26. The particle of claim 24, whereinthe nanoparticle comprises a metal compound selected from the groupconsisting of a metallic sulfide, a metallic arsenide, a metallicselenide, a metallic telluride, a metallic oxide, a metallic halide anda mixture thereof.
 27. The particle of claim 23, wherein thenanoparticle is a semiconductor nanoparticle.
 28. The particle of claim27, wherein the semiconductor nanoparticle comprises cadmium sulfide(CdS), germanium (Ge), silicon (Si), silicon carbide (SiC), selenium(Se), cadmium selenide (CdSe), cadmium telluride (CdTe), zinc sulfide(ZnS), zinc selenide (ZnSe) or zinc oxide (ZnO).
 29. The particle ofclaim 22, wherein A is selected from the group consisting of a thiol, anamine, a phosphine, a phosphate, a borate, a tetra alkyl ammonium, acarboxyl, a silicate, a siloxyl, a selenate, an arsenate and analuminate.
 30. The particle of claim 22, wherein B is selected from thegroup consisting of a thiol, an amine, a phosphine, a carboxyl, asilicate, a siloxyl, a silane, a selenate, an arsenate and an aluminate.31. The particle of claim 22, wherein X is present and is a straightchain, branched or cyclic hydrocarbon selected from the group consistingof alkyl, alkenyl and alkynyl, optionally substituted with a fluoride,chloride, bromide or iodide.
 32. The particle of claim 22, wherein thebifunctional ligand is selected from the group consisting of3-mercaptopropyl trimethoxysilane [SH(CH₂)₃(Si(OMe)₃)] (MPS),1,3-propanedithiol [(HS(CH₂)₃SH)] 3-aminopropanethiol [(HS(CH₂)₃NH₂)](APT) and 3-aminopropyl trimethoxysilane [NH₂(CH₂)₃Si(OMe)₃] (APS). 33.The particle of claim 22, wherein the coating is selected from the groupconsisting of silica (SiO₂), Se, an organic conducting polymer, a metal,a metal oxide, a metal sulfide, a metal selenide, a metal telluride, anda metal halide.
 34. The particle claim 22, wherein the coating issilica.
 35. The particle of claim 33, wherein the coating is a metaloxide selected from the group consisting of titania (TiO₂), zirconia(ZrO₂), alumina Al₂O₃), zinc oxide (ZnO), tin dioxide (SnO₂) ormanganese oxide (MnO).
 36. The particle of claim 33, wherein the coatingis a metal sulfide selected from the group consisting of CdS and ZnS.37. The particle of claim 33, wherein the coating is a metal selenideselected from the group consisting of CdSe and ZnSe.
 38. The particle ofclaim 33, wherein the coating is a metal telluride selected from thegroup consisting of CdTe and ZnTe.
 39. The particle of claim 33, whereinthe source of coating is a metal halide selected from the groupconsisting of silver iodide (AgI) and silver bromide (AgBr).
 40. Theparticle of claim 33, wherein the source of coating is a metal selectedfrom the group consisting of platinum, palladium, iridium, bismuth,copper, silver, gold, and alloys and mixtures thereof.
 41. A method fordetermining the presence of an analyte in a sample suspected ofcontaining the analyte comprising: (a) providing a coatedparticle-ligand composition, wherein the ligand is bound to the coatedparticle and further wherein the coated particle-ligand composition iscapable of specifically binding to the analyte and capable of providinga detectable signal; (b) incubating the sample with the coatedparticle-ligand composition to form a coated particle-ligand:analytecomplex; and (c) detecting the presence of the coatedparticle-ligand:analyte complex as indicating of the presence of theanalyte in the sample and wherein the coated particle comprises acoating attached to said particle via a bifunctional ligand havingstructural formula (I): A—X—B wherein A is a first functional group thatattaches to the particle, or to a coating formed on the particle, B is asecond functional group that activates the surface of the core particlefor nucleation of a coating layer and X is an optional linking group.42. The method of claim 41, wherein the particle is a nanoparticle. 43.The method of claim 42, wherein the nanoparticle is a semiconductornanoparticle.
 44. The method of claim 43, wherein the semiconductornanoparticle comprises cadmium sulfide (CdS), germanium (Ge), silicon(Si), silicon carbide (SiC), selenium (Se), cadmium selenide (CdSe),cadmium telluride (CdTe), zinc sulfide (ZnS), zinc selenide (ZnSe) orzinc oxide (ZnO).
 45. The method of claim 44, wherein the bifunctionalligand is selected from the group consisting of 3-mercaptopropyltrimethoxysilane [SH(CH₂)₃(Si(OMe)₃)] (MPS), 1,3-propanedithiol[(HS(CH₂)₃SH)] 3-aminopropanethiol [(HS(CH₂)₃NH₂)] (APT) and3-aminopropyl trimethoxysilane [NH₂(CH₂)₃Si(OMe)₃] (APS).
 46. The methodof claim 45, wherein the coating is selected from the group consistingof silica (SiO₂), Se, an organic conducting polymer, a metal, a metaloxide, a metal sulfide, a metal selenide, a metal telluride, and a metalhalide.
 47. The method of claim 46, wherein the coating is silica. 48.The method of claim 3 wherein the particle is less than 60 nm andpreferably less than 40 nm.
 49. The method of claim 3 wherein thecoating has a thickness of less than 30 nm.
 50. The particle of claim 23wherein the particle size is less than 60 nm and preferably less than 40nm.
 51. The particle of claim 23 wherein the coating has a thickness ofless than 30 nm.
 52. The method of claim 41 wherein the particles sizeis less than 60 nm and preferably less than 40 nm.
 53. The method ofclaim 41 wherein the coating has a thickness of less than 30 nm.